The overall objective of these studies is to demonstrate the clinical feasibility of using in vivo EPR oximetry to obtain clinically useful information from tumors in patients. In these studies we will focus on the application that will have the most immediate and widespread impact on clinical care, the ability to make repeated non-invasive measurements of tumor pO2. In vivo EPR would be the first clinically applicable technique that has this ability. Our underlying hypothesis is that repeated measurements of pO2 can be used to optimize tumor therapy, especially radiation therapy and/or combined therapy, so that the therapy is applied at times when the therapeutic ratio will be maximized. This capability also will provide very useful measurements of the effectiveness and mode of action of many therapeutic approaches. Thus, the proposed research fits very well with the aim of this R21 to establish the clinical feasibility of a technique that can significantly enhance the efficacy of therapy. The specific aims are: 1. To establish the methodology needed to make valid measurements of tumor pO2 in human subjects under conditions that are compatible with the constraints of clinical practice and comfort of patients. To demonstrate this and to relate the noninvasive EPR measurements of oxygen to invasive techniques that also have the potential for making direct measurements of tumor oxygen in human subjects, we will carry out feasibility studies in healthy volunteers using an appropriate tumor model system. 2. To verify that the measurements can be accomplished in tumors in human subjects. Our hypothesis is that the measurements can be made in patients (patients with cutaneous melanoma lesions) with acceptable data acquisition times and such that robust p02 measurements can be obtained in less than 15 minutes, including setup time, and under conditions that are acceptably within the constraints of clinical practice. 3. To make serial measurements of tumor pO2 in human tumors during the course of radiation therapy and to begin to determine whether the pO2 of tumors will vary during the course of therapy sufficiently to be radiobiologically significant. These measurements will take place in patients undergoing radiation therapy who have lesions that are suitable for the methodology to be employed in these initial studies. Our hypothesis is that human tumors will have responses of oxygen to ionizing radiation similar to those previously demonstrated in animal models. The subaims for these studies include: a. Extending the determination of feasibility to a wider range of sites and types of tumors; b. Determining the feasibility of following changes in pO2 over the full time course of clinical fractionated radiation therapy; c. Determining the feasibility of continuous measurements for up to 120 minutes. [unreadable] [unreadable] [unreadable]